ALPHA-KETO ACID METABOLISM BY HEPATOCYTES CULTURED IN A HYBRID LIVER SUPPORT BIOREACTOR

Isolated pig liver cells cultured using a perfusion technique were ana lyzed over 39 days to test their ability to change the perfusate alpha -keto acid profile. While the pyruvate concentration in the culture me dium decreased as of the first day, the alpha-ketoglutarate (KG), alph a-ketoisocaproate (KIC), alpha-ketoisovalerate (KIV) and alpha-keto-be ta-methyl-n-valerate (KMV) were synthesized immediately and released b y the liver cells. The metabolic capacity of the cell culture system i ncreased up to day 10, decreased during the following 5 days and reach ed a steady state beyond day 15, which was maintained for at least 30 days. The branched chain a-keto acid release, in particular alpha-keto isocaproate, reflects an effective transamination capacity of the newl y developed culture system and shows an intact protein biosynthesis fo r at least 30 days in vitro.